Recombinant human endostatin endostar suppresses angiogenesis and lymphangiogenesis of malignant pleural effusion in mice.

Abstract

BACKGROUND:

Malignant pleural effusion (MPE) is a common complication of lung cancer. One widely used treatment for MPE is Endostar, a recombined humanized endostatin based treatment. However, the mechanism of this treatment is still unclear. The aim of this study was to investigate the effects of Endostar in mice with MPE.

METHODS AND MATERIALS:

Lewis lung carcinoma (LLC) cell line expressing enhanced green fluorescent protein (EGFP) was injected into pleural cavity to establish MPE mice model. Mice were randomly divided into four groups. High dose of Endostar (30 mg/kg), low dose of Endostar (8 mg/kg), normal saline, or Bevacizumab (5 mg/kg) was respectively injected into pleural cavity three times with 3-day interval in each group. Transverse computed tomography (CT) was performed to observe pleural fluid formation 14 days after LLC cells injection. Mice were anesthetized and sacrificed 3 days after final administration. The volume of pleural effusion n was measured using 1 ml syringe. Micro blood vessel density (MVD), Lymphatic micro vessel density (LMVD), the expression level of vascular endothelial growth factor A (VEGF-A) and VEGF-C were observed by immunohistochemistry (IHC) staining.

RESULTS:

The volume of pleural effusion as well as the number of pleural tumor foci, MVD and the expression of VEGF-A were significantly reduced in high dose of Endostar treat group. More importantly, LMVD and the expression of VEGF-C were markedly lower in treat group than those in the other three control groups.

CONCLUSION:

Our work demonstrated that Endostar played an efficient anti-cancer role in MPE through its suppressive effect on angiogenesis and lymphangiogenesis, which provided a certain theoretical basis for the effectiveness of Endostar on the MPE treatment.

• Authors: Xingqun Ma, Yanwen Yao, Dongmei Yuan, Hongbing Liu, Shouju Wang, Changsheng Zhou, Yong Song
• Journal: PloS one (PLoS One) Vol. 7 Issue 12 Pg. e53449 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23285296 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endostatins
• Recombinant Proteins
• enhanced green fluorescent protein
• Green Fluorescent Proteins
• endostar protein

Topics

• Animals
• Carcinoma, Lewis Lung (complications, drug therapy, pathology)
• Cell Line, Tumor
• Down-Regulation (drug effects)
• Drug Evaluation, Preclinical
• Endostatins (pharmacology, therapeutic use)
• Green Fluorescent Proteins (genetics, metabolism)
• Lymphangiogenesis (drug effects, physiology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation
• Neovascularization, Pathologic (etiology, prevention & control)
• Pleural Effusion, Malignant (complications, drug therapy, pathology)
• Recombinant Proteins (pharmacology, therapeutic use)